Breathing during rapid eye movement sleep (REMS) is highly irregular. At times ventilation may fall precipitously, resulting in hypoxemia in patients with sleep-disordered breathing. Despite manipulations of chemical or other afferent information, this variability persists, suggesting that mechanisms producing this instability are intrinsic to the CNS. These irregularities may be the result of behaviors arising in the cortex, the profound atonia of skeletal muscles preventing their expression. Alternatively, the irregularities may originate in the brainstem where normal elements necessary for the generation of REMS are present. Our studies of REMS have shown that even during phasic activity, the diaphragmatic EMG for the majority of breaths is identical to that of tonic REMS and slow wave sleep. Intermittently, particularly during phasic activity, the EMG is either excited or inhibited. In addition, both pontine lesions and changes in O2 and CO2 can affect the magnitude and frequency of these altered breaths. Therefore, we hypothesize that there are at least three influences that summate on phrenic motor nuclei during REMS: a region(s) mediating motor excitation, a region(s) mediating motor inhibition, and the respiratory pattern generator (RPG). Unequal effects on different motoneurons can result in altered magnitude and recruitment patterns. With respect to afferent inputs, each region may be subject to differential stimulation. Whereas the RPG is strongly influenced by chemical drive, the excitatory and inhibitory areas may be part of a system involved in startle responses that is sensitive to alerting stimuli. In addition, breathing during REMS is subject to feedback control; the duration of each breath is inversely related to the level of inspiratory drive to the muscles. To investigate this three-influence hypothesis, we plan to: (1) Examine the role of various brainstem regions in mediating the inhibitions and excitations. We will examine the changes in motor unit recruitment caused by focal stimulations or lesions. (2) Assess the effects of chemical and auditory stimulation on these central influences during REMS. (3) Study the role of the vagus in the control of inspiratory drive and timing. The results should clarify the role of the brainstem in the disordered breathing seen in REMS.